Tourists are told that Tverskaya Street existed as early as the 12th century. Its importance for the medieval city was immense, as it connected Moscow with its superior, and later chief rival, Tver. At that time, the thoroughfare crossed the Neglinnaya River. The first stone bridge across the Neglinnaya was set up in 1595.

In the 17th and 18th centuries, Tverskaya Street was renowned as the centre of Moscow's social life. The nobility considered it fashionable to settle in this district. Among the Palladian mansions dating from the reign of Catherine the Great are the residence of the mayor of Moscow (1778–82, rebuilt in ), and the English Club (1780s). The mayor's residence among a number of other historic buildings was moved about 14 meters for the widening of the Gorky Street during Stalin's time. On the square before it stands a statue of the legendary founder of Moscow, Yuri Dolgoruky, erected for the city's 800th anniversary.[1]

During the imperial period, the importance of the thoroughfare was highlighted by the fact that it was through this street that the tsars arrived from the Northern capital to stay at their Kremlin residence. Several triumphal arches were constructed to commemorate coronation ceremonies. In 1792, the Tverskaya Square was laid out before the residence of the governor of Moscow as a staging ground for mass processions and parades. In 1947, the square was decorated with an equestrian statue of Prince Yury Dolgoruky, founder of Moscow.

Towards the end of the 19th century, the street was reconstructed, with stately neoclassical mansions giving way to grandiose commercial buildings in an eclectic mixture of historical styles. A characteristic edifice of the time is the eclecticHotel National, Moscow (1901-1903), whose interior is a landmark of Russian Art Nouveau. In 1888 the actor, theatre director and founder of the Moscow Art Theatre, Constantin Stanislavski, rented the Ginzburg House on the street and had it converted into a luxurious clubhouse with its own large stage and several exhibition rooms, in order to house his newly formed Society of Art and Literature.[2] The Society gave its last performance there on 3 January 1891 and the building burnt down on the night of January 10.[3]

Further expansion occurred in line with Joseph Stalin's 1935 master plan. During that period, all the churches and most other historic buildings were torn down in order to widen the street and replace low-rise buildings with larger, early Stalinist apartment blocks and government offices. Arkady Mordvinov, who handled this ambitious project, retained some historical buildings, like the ornately decorated Savvinskoye Podvorye by Ivan Kuznetsov. This building was moved to a new foundation North from the new street line, and is now completely enclosed inside Mordvinov's Stalinist block at 6, Tverskaya Street.

The project was only partially completed before World War II; more Stalinist blocks appeared in the 1940s and 1950s, still leaving a lot of 19th-century buildings. Most of them were torn down later, with a few exceptions like Yermolova Theatre still standing. Intourist Hotel, a 23-story tower built in 1970, has been demolished in 2002 and replaced with an equally controversial hotel block.

Tverskaya Street is the most expensive shopping street in Moscow and Russia. According to an index published by global real estate company Colliers International in 2008, it is now the third most expensive street in the world, based on commercial rental fees. It is the center of the city's nightlife and entertainment.

Plans for the reconstruction of the Tverskaya radius into a grade-separated freeway, already under way in remote parts of the route (see Leningradsky Prospekt Reconstruction for a complete schedule), have been authorized for Tverskaya Zastava and Pushkin Square in April, 2007, to be completed in 2009. Work is already underway at the first location. Both squares will acquire complex multi-level, grade-separated crossings and underground shopping malls, despite objections from preservationists and traffic experts.